Migrastatin (1) is a novel 14-membered ring macrolide natural product, that was first isolated from a cultured broth of Streptomyces sp. MK929-43F1 by Imoto et al. (see, Nakae et al., J. Antibiot., 2000, 53, 1130-1136; and Nakae et al., J. Antibiot., 2000, 53, 1228-1230). It was recently reported that cultures of Streptomyces platensis also produce Migrastatin (see, Woo et al., J. Antibiot., 2002, 55, 141-146).

Migrastatin has been shown to inhibit both migration and anchorage-independent growth of human tumor cells (see, Nakae et al., J. Antibiot., 2001, 54, 1104-1107), and has sparked interest in the area of cancer research. Specifically, migration of tumor cells is part of the complex process of metastasis, which is the leading cause of death in cancer patients. Therefore, Migrastatin and derivatives thereof hold great potential as therapeutic agents for the treatment of cancer.
After initial isolation and reporting of this compound, several groups explored the possibility of preparing derivatives and/or further exploring their biological activity. Each of these groups, however, was only able to obtain Migrastatin and derivatives thereof by fermentation techniques and/or by modifications to the natural product, and thus was limited in the number and types of derivatives that could be prepared and/or evaluated for biological activity.
Clearly, there remains a need for compounds related to Migrastatin. Therefore, there is a need to develop synthetic methodologies to access a variety of novel analogues of Migrastatin, particularly those that are inaccessible by making modifications to the natural product. It would also be of particular interest to develop novel compounds that exhibit a favorable therapeutic profile in vivo (e.g., are safe and effective).